November 22, 2012 | 1
“Once the diversity of the microbial world is catalogued… it will make astronomy look like a pitiful science.” Julian Davies
For Neil Armstrong, the giant step for mankind was taken on the moon. For Jeff Leach, it might just be in the colon, at least if he can find the money.
Jeff Leach called me not so long ago to ask me about my colon. Well, that isn’t totally right. He called to tell me about other peoples. Is that worse?
In the colon live trillions of bacteria (though such estimates are guesses as wild as those about the numbers of stars), a universe of planet-sized cells just above the sphincter. These bacteria are important, but uncharted. The most poorly known feature of these beasts is how they vary from one person to the next and why. Your metabolism, immune health, propensity to diabetes and ability to digest seaweed have all, recently, been suggested to depend upon the microbes on or inside you, but on what does the composition of those microbes themselves depend?
This is a version of the belly button mystery I discussed last week—the mystery of what determines just which microbes you have and depend on (or fight). Leach wants to understand what determines the wild life of your colon.
Most readers of Scientific American are aware that their bodies are covered inside and outside with microbes on which his or her life, odor, and much else depend—their cloak of cells. But this consensus is new. In the 1960s Lynn Margulis posited that the mitochondria in our cells and chloroplasts in plant cells were relictual bacteria, evidence of ancient symbioses. She also argued that symbiosis were everywhere, a dominant feature of evolution. She was right on all counts, the founding mother of the microbiome. She was also ignored. Not long after, Carl Woese went into his lab proposing to look at the nucleotides of bacteria to create evolutionary trees of microbes. He was laughed at, but went on to found modern evolutionary biology. Then, in the 1980s, while using LSD and driving around with his girlfriend Kary Mullis had the idea to use the enzymes in an Archaean (a group of microbes that Woese put on a totally unique branch of the tree of life) to amplify DNA and, in essence, produce much more of it for analysis. Together these accomplishments set the stage for the modern field of microbial ecology and evolution. For all of this work, Margulis, Woese and Mullis were regarded as crazy (They were not then, though each of them would ultimately turn to forms of wildness with time. Perhaps when you are once right and no one listens, you can come to believe that every time that no one listens you are right).
Leach wants to take the insights of Margulis and the tools of Woese and Mullis and go big. He is a go big or go home kind of guy. He has the “let’s go kick some butt,” demeanor of a high school wrestling coach one win shy of the state championship. His perspective is that he can only really understand what is going on by seeing samples of feces (from toilet paper wipes) from thousands and thousands of samples. With those samples, Leach wants to study the variation among people in terms of their gut microbes (or at least the ones that end up in feces). With so many samples he might be able to understand the effect of subtle differences among individuals. Are vegan’s microbiomes different from those of vegetarians? Or what effect does having a dog have on your microbiome? Or do probiotics have any effect on the micrbiome at all (they affect rat and mouse microbiomes, but alas rats and mice aren’t the ones buying the stuff)? This sort of ambitiousness is possible only because Leach has teh good fortune to be able to work after the earlier, harder, times. Leach wants to see with the tools he has inherited. Galileo had a telescope. Anton Von Leeuwenhoek had a single-lens microscope. Leach has bundled up pieces of used Charmin, that and modern genetics.
[Image 1. Jeff Leach sampling home and body microbes in Namibia. The home samples are part of our Wild Life of Our Homes project; yourwildlife.org].
Leach thinks that there are healthy microbial communities and sick ones, that most of us tend to have somewhat to very sick ones and if we understand the variation we might understand how to eat, live, and farm (microbes) in such a way as to favor the healthy ones. He wants to study whole families, including cats, dogs and all the rest. This is an exciting idea, but it, like hundreds of other exciting ideas about gut microbes, still needs to be tested. The field is in its stumbling infancy. The field needs the data; Leach needs the data.
Leach is an anthropologist. He specializes in talking to people, not probing them. He needs help and so he has been making phone calls and in a global version of phone tag he has pulled together a super team of microbiologists, and then me, to try to help with his endeavor. The leaders of this large endeavor are now Leach, Rob Knight at the University of Colorado and Jack Gilbert at University of Chicago and Argonne National Lab, but the team is a who is who of the microbial ecologists of the body, intellectual descendents of Margulis, Mullis and Woese. Knight and Gilbert are now leading the technical part of the project and Leach is coordinating its public reach and offering anthropological context. Knight and Gilbert will use fancy molecular tools inspired by Woese and Mullis to see which species are in the feces of those who are sampled and then tell the participants about those species. My job, I think, is to help coordinate what we tell folks about those species. I’m the microbial biographer (stay tuned here for the edited biography)
But here is the problem, a problem we have encountered in our own studies of belly buttons and homes (yourwildlife.org). Microbial ecology and evolution take time. Processing samples is slow and budgets are fixed such that the more people are interested in projects, beyond some limit, the more can be understood about the invisible world, but also the longer it takes to get the job done. Leach had the idea to get around this problem by funding his project via Indiegogo (it sounds like a rash you get from being on Leach’s wrestling team, but it is actually a crowd-funding website). Participants will donate funds to have their samples processed, enough funds to cover the cost of processing their samples (which pays for their piece of a robot, a technician and a postdoc—yes, and this is terrible, the robot gets paid the most). As a starting point, he and Rob Knight have decided that if 275,000 are raised, it will be enough to get the project off the ground (again, damned robot). The project is called American Gut (to be followed, one hopes, by Australian Gut, Thai Gut, etc…, following in American Idol footsteps). You can donate here, but there is also a comment section so if you don’t have the cheddar you can always just leave a note. For a hundred bucks, Leach and crew will tell you what microbes live in you or your dog. For two hundred they will compare them to those in you. Are you more similar in terms of your microbes to your neighbor or your pet? Does it depend on diet? Does it depend on your genes? Does it depend on where you live? To really answer these questions, especially nuanced ones such as the different effects of vegan versus vegetarian diets or the influence of one probiotic over another, they need many, many, people to participate, an unprecedented number of folks, but the advantage of providing samples for donations is that the more people participate the more money is available to the team to do the work.
[Image 2. Rob Knight in his lab at the University of Colorado].
What is interesting and exciting about this project is that, for your money, it does not propose to deliver health miracles, a thinner fitter you or really anything practical in the short term. It proposes instead to produce science, the science of America’s colonic diversity and the science of you. In this era in which science seems to be getting beat up left and right (though mostly right), a time in which the call is to lower taxes and ignore climate change, will Americans pay for such knowledge? Margulis, Woese and Mullis never appear to have gotten their greatest work funded by the federal government. They did it on shoestrings and peanut butter and jelly sandwiches. But what if the work the public is willing to pay for is different from the work that tends to get funded, what if the public cares more about the ecology of their bodies than do review panels? This is just what Leach, Knight and Gilbert are hoping for.
Even if Americans won’t pay for their science there is a back up plan. Leach and crew can offer that thing that seems to have even more cache, a world record. I haven’t checked with Guinness, but I am willing to bet that if Leach can really gets thousands of samples he will have the world’s largest collection of pieces of used toilet paper. If not for science or personal knowledge, you can still support Leach in his quest to be the champ.
As for Margulis, Woese, and Mullis… Woese continues to work. Mullis gives lectures. Margulis died last year. I can’t help wondering what she in particular would think of this and other microbiome projects. Her edited biography has just been released. Reading it reminds me of her reckless intellect, but also her battles. She fought her whole life to do what she loved, to study the microbes that she thought (rightly) run and own the world. Now the grandeur and importance of those same microbes have been recognized, enough so that athletes want to know about their microbes and celebrities do too. I have to hope Margulis would want to be sampled, to see her own trillions of symbionts. I think she would; toward the end of her life she was delighted to find a new species of single-celled beast in the pond where she liked to skinny dip. It had been swimming with her all those years, her private mystery. Would that we could have found a new species lurking in her gut too. But the reason I really wish she were still around is to help us think wildly about the data that result from Leach’s samples and those from other projects like our belly button or homes projects, to see the answers so outrageous that even once we articulate them no one will believe them for tens of years.
Giving thanks: Thank you Lynn Margulis, Carl Woese and Kary Mullis for letting us see what was so long invisible. Thank you invisible microbes for letting us exist.